• Gin S Malhi, Philip B Mitchell, and Shahzad Salim.
• School of Psychiatry, University of New South Wales, Randwick, Sydney, New South Wales, Australia.
• Cns Drugs. 2003 Jan 1;17(1):9-25.

AbstractBipolar depression is the predominant abnormal mood state in bipolar disorder. However, despite the key pertinence of this phase of the condition, the focus of research and indeed of clinical interest in the management of bipolar disorder has been mainly on mania. Bipolar depression has been largely neglected, and early studies often failed to distinguish depression due to major unipolar depression from that due to bipolar disorder. Consequently, many treatments used in the management of major depression have been adopted for use in bipolar depression without any robust evidence of efficacy. The selective serotonin reuptake inhibitors (SSRIs), bupropion, tricyclic antidepressants and monoamine oxidase inhibitors are all effective antidepressants in the management of bipolar depression. They are all associated with a small risk of antidepressant-induced mood instability. The mood stabilisers lithium, carbamazepine and valproate semisodium (divalproex sodium) all appear to have modest acute antidepressant properties. Among these, lithium is supported by the strongest data, but the use of lithium in the treatment of bipolar depression as a monotherapeutic agent is limited by its slow onset of action. Recently, there has been a growing body of evidence suggesting that lamotrigine may have particular effectiveness in both the acute and prophylactic management of bipolar depression. Clinical management of bipolar depression involves various combinations of antidepressants and mood stabilisers and is partly determined by the context in which the depressive episode occurs. In general, 'de novo' and 'breakthrough' (where the patient is already receiving medication) bipolar depression may be successfully managed by initiating mood stabiliser monotherapy, to which an antidepressant or second mood stabiliser may be added at a later date, if necessary. Breakthrough episodes of bipolar depression occurring in patients receiving combination therapy (two mood stabilisers or a mood stabiliser plus an antidepressant) require either switching of ongoing medications or further augmentation. If this fails, then novel strategies or ECT should be considered. Bipolar depression is a disabling illness and the predominant mood state for the vast majority of those with bipolar disorder. It therefore warrants prompt management once suitably diagnosed, especially as it is associated with a considerable risk of suicide and in the majority of instances is eminently treatable.

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